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Oral anticoagulants (AC) and antiplatelet (AP) agents are increasingly prescribed to prevent and treat acute and chronic thrombotic conditions. The direct oral anticoagulants (DOAC), a newer class of AC, raise concerns in the trauma setting. Our study aims to compare the mortality rates and other outcomes among adult trauma patients based on pre-admission AC/AP status. We conducted a retrospective cohort study of a prospectively collected database of trauma patients previously on DOAC, warfarin, aspirin or clopidogrel. A matched control group of trauma patients not receiving AC/AP was used for comparison. Our primary endpoint was in-hospital mortality according to antithrombotic medication class. Secondary endpoints included length of stay (LOS), intensive care unit (ICU) admission, need for blood transfusion, and discharge to a dependent setting. Univariate and multivariate analyses were conducted. There were 996 exposed patients and 234 controls, with no major clinically significant difference among study groups in terms of gender, injury site, injury severity, mechanism, and comorbidities. The mortality rates were 2.14% (control, 5/234), 2.88% (DOAC, 3/104), 3.34% (aspirin, 17/509), 7.63% (warfarin, 18/236), 9% (clopidogrel, 8/89), and 13.79% (aspirin + clopidogrel, 8/58) (p

To collect and summarize pregnancy outcomes among women with a history of cerebral sinus vein thrombosis (CSVT). A retrospective multicenter case–control study. The study group comprised all women diagnosed with CSVT during 2004–2018 at four university hospitals, and with follow-up data of pregnancy. A control group of women with a singleton pregnancy was established by matching, four-to-one, according to maternal age. The data of 74 pregnancies of 65 women with CSVT were analyzed. The median time-to-pregnancy interval from the CSVT was 4.2 [2.7–6.8] years. Anticoagulation therapy in the form of enoxaparin was administered in 68 (91.9%) pregnancies. Adjunctive low-dose aspirin was used throughout 12 (16.2%) pregnancies. Overall, 54 (73.0%) of the pregnancies ended in live births and 20 (27.0%) in miscarriage. The use of anticoagulation therapy during pregnancy was positively associated with live birth outcome (P

Postpartum low-molecular-weight heparin (LMWH) thromboprophylaxis is indicated for a substantial proportion of women. We assessed women’s adherence to postpartum thromboprophylaxis and the factors associated with adherence. This retrospective cohort study was conducted at a university hospital during 2018. Parturients for whom a recommendation for LMWH prophylaxis was given at discharge from the maternity ward were contacted at the end of the recommended post-discharge course of LMWH, and were invited to participate in a telephone survey. The main outcome measures were optimal (> 80%) and suboptimal adherence (

Direct oral anticoagulants (DOACs) are commonly administered at a level that is lower than that recommended by dose reduction criteria. This raises concern regarding the adequacy of anticoagulation achieved. To evaluate the relationship between inappropriate dosing and DOAC levels. Medical records of atrial fibrillation patients who underwent DOAC level testing during 2013-2017 were reviewed. The primary outcomes were drug levels under and above the expected steady-state range, and in the lowest and highest quartiles. Of 143 patients who underwent DOAC measurements, only 87 (60.8%) received the appropriate dose. Levels under the expected range and in the lowest quartile were found in 11.9% and 15.0% of patients treated with appropriate dosing compared to 21% and 41.5% of patients treated with inappropriately low dose. DOAC levels were above the expected range and in the highest quartile in 23.8% and 32.5% of patients treated with the appropriate dose compared to 7.1% and 9.4% treated with inappropriately low dose. In multivariate analysis, the administration of an appropriate DOAC dose was associated with a lower rate of DOAC in the lowest level (adjusted odds ratio [95% CI] 0.30 (0.12, 0.76), P = 0.011). On the other hand, appropriate dose was associated with drug levels in the highest quartile (odds ratio [95% CI] 3.77 (0.12, 0.76), P = 0.011). Treatment with inappropriately low DOAC dosing compared to appropriate dose is associated with lower DOAC levels. However, among those treated with appropriate dosing, a higher proportion had high DOAC levels above the expected range.

Little is known regarding the management of direct oral anticoagulants (DOACs) in patients with enzyme-inducing drugs (EID). The use of EID may lead to sub-therapeutic concentrations of DOACs and to treatment failure. Thus, many patients on EIDs cannot benefit from the advantages of DOACs. This was a retrospective study, evaluating the management of hospitalized patients with DOACs. Characteristics of hospitalized patients with a prescription for DOACs, with and without EIDs, were summarized and evaluated, and management strategies addressing the potential interaction were documented, including the use of DOAC concentration monitoring. During the period evaluated, 1596 hospitalized patients with prescriptions for DOACs were identified. Most patients received apixaban (n = 1227, 77%), followed by rivaroxaban (240, 15%), and dabigatran (129, 8%). Twenty-two patients (1.4%) had concomitant EIDs. Demographic and clinical characteristics of hospitalized patients with DOACs were similar in those receiving EID and those not. Management strategies included stopping DOAC or EID (41%), and DOAC dose increase (14%). During management of these interactions, DOAC concentrations were measured for 11 of 22 patients and were below the 5th percentile of expected concentration for six of these patients. The management of patients with DOAC concentration measurement differed significantly from those without (p = 0.005), as they were much less likely to have one of the medications stopped and more often had the DOACs' dose increased. Among hospitalized patients with DOACs, EIDs are not rare. DOAC concentrations are often low in the presence of EIDs. DOAC concentration monitoring may be useful in settings requiring both DOAC and EIDs.

Antiphospholipid syndrome (APLS) is caused by antiphospholipid autoantibodies, and manifests with vascular and/or obstetric complications. The factors associated with initial disease presentation and course are unknown. We assessed the antibody profile associated with disease presentation and with the development of vascular and obstetric complications in women with initially vascular or initially obstetric APLS. A review of records of APLS women at childbearing age followed at one center during 2006-2015. Of 126 women, median age at diagnosis 29 [23-37] years, 62 were initially diagnosed with purely obstetric APLS and 64 with purely vascular APLS. Baseline characteristics and antibody profile did not differ according to the initial diagnosis. At a mean follow-up duration of 61 ± 23 months, 19 (30.6%) with initially obstetric disease, and 20 (31.3%) with initially vascular disease, developed vascular and obstetric complications, respectively (P = 1.0). Among those with triple positivity [lupus anticoagulant (LAC)+, anticardiolipin (ACL)+, anti beta2-glycoprotein I (AB2GPI)+], a higher proportion developed both obstetric and vascular complications, compared to those with single or double positivity (42.3 vs. 16.4%, P = 0.002). In multivariate analysis, the presence of LAC (P = 0.008), ACL IgG (P = 0.009) or AB2GPI IgG (P = 0.01) was the only independent predictor of the development of both obstetric and vascular complications. Almost one-third of women with initially vascular or initially obstetric APLS developed mixed disease. The antibody profile was the only prognostic marker for disease course. The association found between LAC, ACL IgG or AB2GPI IgG, and patient outcomes could contribute to risk stratification and individualized patient management.

To investigate the course of acquired type 2A von Willebrand syndrome (AVWS) in relation to patient management and outcomes among pregnant patients with essential thrombocytosis (ET). A review of pregnant women with ET evaluated for AVWS at the beginning of pregnancy and at the third trimester. Eighteen women with 24 pregnancies were included in this study. A history of bleeding was noted in 8 (44%) patients. In 20 (83%) pregnancies AVWS was evident at the initial testing. Following initial testing, antithrombotic therapy was administered in 22 (92%) pregnancies (aspirin, n = 20 and low-molecular-weight heparin, n = 2). In the remaining two pregnancies, VWF:RCo levels were below 30%; thus, aspirin was given only after repeat testing at 14–16 weeks. At third trimester testing, median VWF:RCo levels were significantly higher than at the initial testing (86 vs. 48%, P

The role of drug-level monitoring among patients using direct-acting oral anticoagulant (DOAC) is unclear. We aimed to investigate its ‘real-life’ utilization and effect on clinical management. A review of records of patients who underwent DOAC level testing during 2013–2017. Overall, 212 patients (median age 77 years) underwent 292 DOAC measurements [apixaban (n = 147), rivaroxaban (n = 102), dabigatran (n = 43)]. Monitoring volume increased by 460% during study period. DOAC level testing was performed during routine follow-up in 51 (17.5%) cases, whereas the remaining 241 (82.5%) measurements were performed due to selected clinical circumstances, most commonly: bleeding (n = 60), perioperative status (n = 45), breakthrough thrombosis (n = 37) and renal failure (n = 35). Drug levels were within the expected range in 210 (71.9%), above the expected range in 62 (21.2%) and lower than expected range in 20 (6.8%). In multivariate analysis, older age (P = 0.005), lower glomerular filtration rate (P = 0.001) and lower body mass index (P = 0.006) were associated with DOAC levels above the expected range. Clinical decisions were affected by DOAC monitoring following most (140/241, 58.1%) measurements for which we identified an indication for testing; yet only rarely when monitoring was performed during routine follow-up (7.8%, 4/51) (P

Stroke and thromboembolic events occurring among patients taking direct oral anticoagulants (DOACs) have been associated with low concentrations of DOACs. Enzyme-inducing antiseizure medications (EI-ASMs) are associated with enhanced cytochrome-P450-mediated metabolism and enhanced P-glycoprotein-mediated transport.The aim of this study was to evaluate the effect of concomitant EI-ASM use on DOAC peak concentrations in patients treated in clinical care.We performed a retrospective cohort study of patients treated with DOACs for atrial fibrillation and venous thromboembolic disease in an academic general hospital. In total, 307 patients treated with DOACs between August 2015 and January 2020 were reviewed. Clinical characteristics and peak DOAC plasma concentrations of patients co-treated with an EI-ASM were compared with those of patients not treated with an EI-ASM. An apixaban dose score (ADS) was defined to account for apixaban dosage and the number of apixaban dose-reduction criteria.In total, 177 peak DOAC plasma concentrations (including apixaban, rivaroxaban, and dabigatran) from 131 patients were measured, including 24 patients co-treated with an EI-ASM and 107 controls not treated with an EI-ASM. The proportion of patients with DOAC concentrations below the expected range was significantly higher among EI-ASM users than among patients not taking an EI-ASM (37.5 vs. 9.3%, respectively; p = 0.0004; odds ratio 5.82; 95% confidence interval [CI] 2.03-16.66). Most of these patients were treated with apixaban (85%); however, sensitivity analysis results were also significant (p = 0.031) for patients with non-apixaban DOACs. In patients co-treated with apixaban and an EI-ASM, median apixaban peak concentration was 106 ng/mL (interquartile range [IQR] 71-181) compared with 150 ng/mL (IQR 94-222) in controls (p = 0.019). In multivariable analysis, EI-ASM use was associated with 6.26-fold increased odds for apixaban concentration below the expected range (95% CI 2.19-17.90; p = 0.001). Apixaban concentrations were significantly associated with EI-ASM use, moderate enzyme inhibitor use, and ADS.Concurrent EI-ASM and DOAC use presents a possible risk for DOAC concentrations below the expected range. The clinical significance of the interaction is currently unclear.

To evaluate the impact of an institutional protocol on patterns of use and outcomes of inferior vena cava filters (IVCF). Following a multidisciplinary effort, an institutional protocol involving dedicated follow-up of patients receiving IVCF and a physician education program regarding IVCF utilization, was established. We prospectively collected data of patients who received IVCF during 2015–2016, following protocol implementation (POST group). For comparison, we reviewed records of patients who received IVCF during 2009–2014, before implementation of the institutional protocol (PRE group). In the PRE and POST groups, 76 and 38 IVCF per year were inserted respectively, with an overall decrease of 50%. IVCF were more likely to be placed for therapeutic rather than prophylactic indications in the POST compared to the PRE group (P = 0.003). Follow-up rates at our coagulation clinic were significantly higher in the POST than the PRE group (100 vs. 22.9%, P

Introduction In the past decade, direct-acting oral anticoagulants (DOAC) have been introduced to medical practice for several indications, with a wide range of dosing regimens. As both over- and under-dosing might lead to life-threatening events, development of methods promoting safe and effective utilization of these agents is imperative. The Hadassah Clinical Pharmacy team initiated a hospital-wide program, for monitoring and promoting safe and effective prescription of DOAC during hospitalization. This study describes the types of drug related problems addressed and the program’s performance in terms of consultation rates and physician acceptance. Methods Electronic medical records throughout the hospital were screened for DOAC orders. All DOAC orders were assessed by a clinical pharmacist for potentially-inappropriate prescribing. When potentially-inappropriate prescribing or a drug-related problem was identified, the clinical pharmacist provided consultation on management options. In specific cases, additional guidance was provided by coagulation and pharmacology specialists. Data on patient characteristics, clinical pharmacist consultations, and physician response was retrospectively retrieved for the first six months of 2017. Characteristics of patients with and without consultations were compared, consultations were categorized by the recommended management of the drug related problem, and physician acceptance rates were evaluated by category. Results During the evaluated period, 585 patients with DOAC orders were identified. Patients were evenly distributed by gender, and age averaged 78 years. Most patients received apixaban (75%) followed by rivaroxaban (14%) and dabigatran (11%), and most (63%) received “reduced dose” regimens. Clinical pharmacists provided 258 consultations for 210 patients, regarding anticoagulation management, such that more than one in three patients on DOAC had potentially inappropriate prescribing or drug related problems. Consultations included alerts regarding potentially inappropriate DOAC doses and recommendations to increase (29%) or decrease (5%) the dose, potentially inappropriate concomitant antiplatelet agents (20%), need for DOAC level monitoring (23%), and alerts regarding other drug related problems (23%). More than 70% of recommendations were accepted by the attending physician. Conclusion Due to the complexity of DOAC management, potentially-inappropriate prescribing and drug related problems are common. Multidisciplinary collaborative projects including review and consultation by clinical pharmacists are an effective method of improving management of patients on DOAC. Trial registration Retrospectively registered at clinicaltrials.gov, NCT03527615.

Inherited afibrinogenemia and hypofibrinogenemia are rare bleeding disorders characterized by markedly reduced levels of fibrinogen in blood. Thrombotic complications in these disorders have been rarely described. We performed a multicenter retrospective study and reviewed the occurrence of thrombotic complications among patients with inherited fibrinogen deficiency. Cases were identified during a review of medical records of all patients with inherited fibrinogen deficiency followed at three different university hospitals in Israel. Nine patients were included in this study: five were afibrinogenemic and four hypofibrinogenemic. There were seven thrombotic events, mostly venous, that occurred in four out of nine patients (44 %). All thrombotic events occurred in afibrinogenemic patients. Mean age at the time of thrombosis was 45 (range 28-61) years. Thrombophilic evaluation performed was negative in all cases. At the time of thrombosis in five out of seven (71.4 %) events, fibrinogen replacement therapy was concurrently given. Therapeutic approach was different among patients ranging from supportive therapy alone, antiplatelet agents and anticoagulant therapy with the concurrent administration of fibrinogen replacement therapy. This study discloses a high rate of thrombosis in patients with afibrinogenemia. Events were both venous and arterial and may be recurrent. Management is highly problematic due to the precarious balance between bleeding and thrombotic risk in these patients. Fibrinogen replacement therapy should be cautiously used in these patients as most thrombotic events followed the administration of fibrinogen replacement therapy. Larger cohorts are warranted to better characterize the best management strategy in these paradoxical events.